Influence of formulation composition and processing on the content uniformity of low-dose tablets manufactured at kilogram scale

Abstract

The purpose of this study was to investigate the impact of processing, API loading, and formulation composition on the content uniformity of low-dose tablets made using direct compression (DC) and roller compaction (RC) methods at 1 kg scale. Blends of 1:1 microcrystalline cellulose/lactose or 1:1 microcrystalline cellulose/dicalcium phosphate anhydrous with active pharmaceutical ingredient (API) at loadings of 0.2, 1 and 5% were processed either by DC or RC. A statistical analysis showed that DC produced comparable content uniformity results to RC. Microcrystalline cellulose/lactose formulations had improved average potency compared to microcrystalline cellulose/dicalcium phosphate anhydrous formulations for both DC and RC. The impact of segregation in the DC blends and adhesion to equipment surfaces was assessed to aid in understanding potency trends. DC may be as suitable as RC for low-dose regime (e.g. < 1 mg) when manufacturing clinical supplies at small scale provided the API has a suitable particle size and potency loss to equipment is negligible.

Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review

“…Generally, dry granulated batches were characterized by lower content RSD; however, the difference did not reach statistical significance. Similar tendencies were observed in segregation tests of the blends using the ASTM type tester, in which the direct compression mixture segregated only under forced conditions of dual hopper filling [80]. Kushner et al carried out manufacturability assessments, aimed at establishing the design space for various tablet CQAs, including content uniformity.…”